7 results on '"Centrón-Broco, Alvaro"'
Search Results
2. CircAFF1 Is a Circular RNA with a Role in Alveolar Rhabdomyosarcoma Cell Migration.
- Author
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Centrón-Broco, Alvaro, Rossi, Francesca, Grelloni, Chiara, Garraffo, Raffaele, Dattilo, Dario, Giuliani, Andrea, Di Timoteo, Gaia, Colantoni, Alessio, Bozzoni, Irene, and Beltran Nebot, Manuel
- Subjects
CIRCULAR RNA ,CELL migration ,RHABDOMYOSARCOMA ,CELL adhesion ,CELL lines ,CELL adhesion molecules - Abstract
Circular RNAs (circRNAs), covalently closed RNAs that originate from back-splicing events, participate in the control of several processes, including those that occur in the development of pathological conditions such as cancer. Hereby, we describe circAFF1, a circular RNA overexpressed in alveolar rhabdomyosarcoma. Using RH4 and RH30 cell lines, a classical cell line models for alveolar rhabdomyosarcoma, we demonstrated that circAFF1 is a cytoplasmatic circRNA and its depletion impacts cell homeostasis favouring cell migration through the downregulation of genes involved in cell adhesion pathways. The presented data underline the importance of this circular RNA as a new partial suppressor of the alveolar rhabdomyosarcoma tumour progression and as a putative future therapeutic target. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
3. The m6A reader YTHDC1 and the RNA helicase DDX5 control the production of rhabdomyosarcoma-enriched circRNAs.
- Author
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Dattilo, Dario, Di Timoteo, Gaia, Setti, Adriano, Giuliani, Andrea, Peruzzi, Giovanna, Beltran Nebot, Manuel, Centrón-Broco, Alvaro, Mariani, Davide, Mozzetta, Chiara, and Bozzoni, Irene
- Subjects
RNA helicase ,CIRCULAR RNA ,PRODUCTION control ,RNA metabolism ,SARCOMA ,TRIGONOMETRIC functions - Abstract
N6-Methyladenosine (m
6 A) is well-known for controlling different processes of linear RNA metabolism. Conversely, its role in the biogenesis and function of circular RNAs (circRNAs) is still poorly understood. Here, we characterize circRNA expression in the pathological context of rhabdomyosarcoma (RMS), observing a global increase when compared to wild-type myoblasts. For a set of circRNAs, such an increase is due to the raised expression of the m6 A machinery, which we also find to control the proliferation activity of RMS cells. Furthermore, we identify the RNA helicase DDX5 as a mediator of the back-splicing reaction and as a co-factor of the m6 A regulatory network. DDX5 and the m6 A reader YTHDC1 are shown to interact and to promote the production of a common subset of circRNAs in RMS. In line with the observation that YTHDC1/DDX5 depletion reduces RMS proliferation, our results provide proteins and RNA candidates for the study of rhabdomyosarcoma tumorigenicity. Rhabdomyosarcoma (RMS) is the most diffused soft tissue sarcoma in children and adolescents. Herein, the authors identify the m6 A machinery and the RNA helicase DDX5 as factors responsible for the increase of a subset of circRNAs in RMS, providing protein and RNA candidates for the study of its tumorigenicity. [ABSTRACT FROM AUTHOR]- Published
- 2023
- Full Text
- View/download PDF
4. CircVAMP3: A circRNA with a Role in Alveolar Rhabdomyosarcoma Cell Cycle Progression.
- Author
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Rossi, Francesca, Centrón-Broco, Alvaro, Dattilo, Dario, Di Timoteo, Gaia, Guarnacci, Marco, Colantoni, Alessio, Beltran Nebot, Manuel, and Bozzoni, Irene
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CIRCULAR RNA , *CELL cycle , *RHABDOMYOSARCOMA , *NON-coding RNA , *RNA modification & restriction , *CELL lines - Abstract
Circular RNAs (circRNAs), a class of covalently closed RNAs formed by a back-splicing reaction, have been involved in the regulation of diverse oncogenic processes. In this article we describe circVAMP3, a novel circular RNA overexpressed in RH4, a representative cell line of alveolar rhabdomyosarcoma. We demonstrated that circVAMP3 has a differential m6A pattern opposed to its linear counterpart, suggesting that the two isoforms can be differently regulated by such RNA modification. Moreover, we show how circVAMP3 depletion in alveolar rhabdomyosarcoma cells can impair cell cycle progression, through the alteration of the AKT-related pathways, pointing to this non-coding RNA as a novel regulator of the alveolar rhabdomyosarcoma progression and as a putative future therapeutic target. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
5. Modulation of circRNA Metabolism by m6A Modification.
- Author
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Di Timoteo, Gaia, Dattilo, Dario, Centrón-Broco, Alvaro, Colantoni, Alessio, Guarnacci, Marco, Rossi, Francesca, Incarnato, Danny, Oliviero, Salvatore, Fatica, Alessandro, Morlando, Mariangela, and Bozzoni, Irene
- Abstract
N
6 -methyladenosine (m6 A) is an RNA modification well-known for its contribution to different processes controlling RNA metabolism, including splicing, stability, and translation of mRNA. Conversely, the role of m6 A on the biogenesis and function of circular RNAs (circRNAs) has yet to be addressed. circRNAs belong to a class of covalently closed transcripts produced via a back-splicing reaction whereby a downstream 5′ splice donor site fuses to an upstream 3′ splice acceptor site. Starting from circ-ZNF609 as a study case, we discover that specific m6 As control its accumulation and that METTL3 and YTHDC1 are required to direct the back-splicing reaction. This feature is shared with other circRNAs because we find a significant direct correlation among METTL3 requirement, YTHDC1 binding, and the ability of m6 A exons to undergo back-splicing. Finally, because circ-ZNF609 displays the ability to be translated, we show that m6 A modifications, through recognition by YTHDF3 and eIF4G2, modulate its translation. • Specific m6 As control accumulation of a subset of circRNAs • METTL3 and YTHDC1 are required to direct the biogenesis of a subset of circRNAs • circRNAs affected by METTL3 YTHDC1 display specific m6 A signatures • circ-ZNF609 translation is modulated through recognition by YTHDF3 and eIF4G2 The role of m6 A in the biogenesis and function of circRNAs has yet to be addressed. We discovered that METTL3 and YTHDC1 modulate the biogenesis of a subset of circRNAs, including circ-ZNF609. We show that m6 A regulates circZNF609 translation via YTHDF3 and eIF4G2. [ABSTRACT FROM AUTHOR]- Published
- 2020
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6. Circular RNA ZNF609/CKAP5 mRNA interaction regulates microtubule dynamics and tumorigenicity.
- Author
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Rossi, Francesca, Beltran, Manuel, Damizia, Michela, Grelloni, Chiara, Colantoni, Alessio, Setti, Adriano, Di Timoteo, Gaia, Dattilo, Dario, Centrón-Broco, Alvaro, Nicoletti, Carmine, Fanciulli, Maurizio, Lavia, Patrizia, and Bozzoni, Irene
- Subjects
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CIRCULAR RNA , *MICROTUBULES , *MESSENGER RNA , *NUCLEIC acids , *RNA-binding proteins , *TUMOR growth - Abstract
Circular RNAs (circRNAs) are widely expressed in eukaryotes and are regulated in many biological processes. Although several studies indicate their activity as microRNA (miRNA) and protein sponges, little is known about their ability to directly control mRNA homeostasis. We show that the widely expressed circZNF609 directly interacts with several mRNAs and increases their stability and/or translation by favoring the recruitment of the RNA-binding protein ELAVL1. Particularly, the interaction with CKAP5 mRNA, which interestingly overlaps the back-splicing junction, enhances CKAP5 translation, regulating microtubule function in cancer cells and sustaining cell-cycle progression. Finally, we show that circZNF609 downregulation increases the sensitivity of several cancer cell lines to different microtubule-targeting chemotherapeutic drugs and that locked nucleic acid (LNA) protectors against the pairing region on circZNF609 phenocopy such effects. These data set an example of how the small effects tuned by circZNF609 /CKAP5 mRNA interaction might have a potent output in tumor growth and drug response. [Display omitted] • circZNF609 interacts with CKAP5 , UPF2 , and SRRM1 mRNAs in vivo • circZNF609-mRNA interaction increases ELAVL1 loading on the mRNAs • ELAVL1 loading by circZNF609 regulates stability and translation of its targets • CAKP5 regulation alters MT dynamics, sensitizing cells to chemotherapeutic drugs In this article, Rossi et al. provide an interesting mechanism in which circZNF609-mRNA interaction increases translation, and among them, CKAP5 is a key factor in microtubule dynamics stability. The authors show how the disruption of RNA-RNA interactions is able to alter microtubule dynamics, sensitizing rhabdomyosarcoma cells to chemotherapeutic drugs. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
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7. Modulation of circRNA Metabolism by m 6 A Modification.
- Author
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Di Timoteo G, Dattilo D, Centrón-Broco A, Colantoni A, Guarnacci M, Rossi F, Incarnato D, Oliviero S, Fatica A, Morlando M, and Bozzoni I
- Subjects
- Adenosine metabolism, Alternative Splicing, Child, Preschool, Female, HEK293 Cells, HeLa Cells, Humans, Male, Nerve Tissue Proteins, RNA Splicing Factors, Adenosine analogs & derivatives, Methyltransferases metabolism, RNA, Circular metabolism
- Abstract
N
6 -methyladenosine (m6 A) is an RNA modification well-known for its contribution to different processes controlling RNA metabolism, including splicing, stability, and translation of mRNA. Conversely, the role of m6 A on the biogenesis and function of circular RNAs (circRNAs) has yet to be addressed. circRNAs belong to a class of covalently closed transcripts produced via a back-splicing reaction whereby a downstream 5' splice donor site fuses to an upstream 3' splice acceptor site. Starting from circ-ZNF609 as a study case, we discover that specific m6 As control its accumulation and that METTL3 and YTHDC1 are required to direct the back-splicing reaction. This feature is shared with other circRNAs because we find a significant direct correlation among METTL3 requirement, YTHDC1 binding, and the ability of m6 A exons to undergo back-splicing. Finally, because circ-ZNF609 displays the ability to be translated, we show that m6 A modifications, through recognition by YTHDF3 and eIF4G2, modulate its translation., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2020
- Full Text
- View/download PDF
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